Gut and liver T cells of common clonal origin are detected in primary sclerosing cholangitis-inflammatory bowel disease

Background & Aims: Recruitment of gut-derived memory T cells to the liveris believed to drive hepatic inflammation in primary sclerosing cholangitis(PSC). However, whether gut-infiltrating and liver-infiltrating T cells share Tcellreceptors (TCRs) and antigenic specificities is unknown. We used pairedgut and liver samples from PSC patients with concurrent inflammatory boweldisease (PSC-IBD), and normal tissue samples from colon cancer controls, toassess potential T-cell clonotype overlap between the two compartments.Methods: High-throughput sequencing of TCRβ repertoires was applied onmatched colon, liver and blood samples from patients with PSC-IBD (n=10),and on paired tumor-adjacent normal gut and liver tissue samples from coloncancer patients (n=10).Results: An average of 9.7% (range: 4.7–19.9%) memory T-cell clonotypesoverlapped in paired PSC-IBD affected gut and liver samples, after excludingclonotypes present at similar frequencies in blood. Shared clonotypesconstituted on average 16.0% (range: 8.7–32.6%) and 15.0% (range: 5.9–26.3%) of the liver and gut memory T cells, respectively. A significantly higheroverlap was observed between paired PSC-IBD affected samples (8.7%,p=0.0007) compared to paired normal gut and liver samples (3.6%), afterdownsampling to equal number of reads.Conclusion: Memory T cells of common clonal origin were detected in pairedgut and liver samples of patients with PSC-IBD. Our data indicate that this isrelated to PSC-IBD pathogenesis, suggesting that memory T cells driven byshared antigens are present in the gut and liver of PSC-IBD patients. Ourfindings support efforts to therapeutically target memory T-cell recruitment inPSC-IBD.